This research project will study the interrelationship among platelets, vessel wall, humoral coagulation factors and plasma proteinase inhibitors which are fundamental to the thrombotic process. The investigation of these interrelationships through a multifaceted, interdisciplinary approach will result in more effective prevention, diagnosis and treatment of thrombotic disease. Specific studies include the partial characterization of the platelet receptor for von Willebrand factor and the effect of von Willebrand factor on platelet-vessel wall interactions, the relationships between the platelet-active von Willebrand factor and the normal and injured vascular endothelial surface in the development of experimental atherosclerosis in swine, the relationships between lipoprotein metabolism and platelet function in the development of atherosclerosis, the definition of the mechanisms by which peptide growth factors stimulate replication in smooth muscle cells, the elucidation of the role of various intracellular messengers in the platelet function, the interaction of plasma proteinase inhibitors with thrombin, factor IXa and factor Xa, the examination of the molecular mechanism of action of heparin as an anticoagulant, physical biochemical studies of the interaction of fibrin with other components of plasma and a study of the interaction of fibronectin (cold-insoluble globulin) with fibrin. The project also contains a clinical core unit which will serve as a resource to the overall program in providing a mechanism for the facile "translation" of basic science information into clinical treatment.